The current standard induction therapy for antineutrophil cytoplasm antibody (ANCA)–associated vasculitis is the combination of high-dose glucocorticoids and cyclophosphamide or rituximab. Although these regimens have high remission rates, they are associated with considerable adverse events presumably due to high-dose glucocorticoids.
Objective
To compare efficacy and adverse events between a reduced-dose glucocorticoid plus rituximab regimen and the standard high-dose glucocorticoid plus rituximab regimen in remission induction of ANCA-associated vasculitis.
Design, Setting, and Participants
This was a phase 4, multicenter, open-label, randomized, noninferiority trial. A total of 140 patients with newly diagnosed ANCA-associated vasculitis without severe glomerulonephritis or alveolar hemorrhage were enrolled between November 2014 and June 2019 at 21 hospitals in Japan. Follow-up ended in December 2019.
Interventions
Patients were randomized to receive reduced-dose prednisolone (0.5 mg/kg/d) plus rituximab (375 mg/m2/wk, 4 doses) (n = 70) or high-dose prednisolone (1 mg/kg/d) plus rituximab (n = 70).
Main Outcomes and Measures
The primary end point was the remission rate at 6 months, and the prespecified noninferiority margin was −20 percentage points. There were 8 secondary efficacy outcomes and 6 secondary safety outcomes, including serious adverse events and infections.
Results
Among 140 patients who were randomized (median age, 73 years; 81 women [57.8%]), 134 (95.7%) completed the trial. At 6 months, 49 of 69 patients (71.0%) in the reduced-dose group and 45 of 65 patients (69.2%) in the high-dose group achieved remission with the protocolized treatments. The treatment difference of 1.8 percentage points (1-sided 97.5% CI, −13.7 to ∞) between the groups met the noninferiority criterion (P = .003 for noninferiority). Twenty-one serious adverse events occurred in 13 patients in the reduced-dose group (18.8%), while 41 occurred in 24 patients in the high-dose group (36.9%) (difference, −18.1% [95% CI, −33.0% to −3.2%];P = .02). Seven serious infections occurred in 5 patients in the reduced-dose group (7.2%), while 20 occurred in 13 patients in the high-dose group (20.0%) (difference, −12.8% [95% CI, −24.2% to −1.3%];P = .04).
Conclusions and Relevance
Among patients with newly diagnosed ANCA-associated vasculitis without severe glomerulonephritis or alveolar hemorrhage, a reduced-dose glucocorticoid plus rituximab regimen was noninferior to a high-dose glucocorticoid plus rituximab regimen with regard to induction of disease remission at 6 months.
Objective We aimed to determine the prevalence and risk factors for osteonecrosis of the femoral head (ONFH) in a multicentre cohort of patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV). Methods One hundred and eighty-six AAV patients who underwent radiographs and MRI screening of bilateral hip joints at more than 6 months after initial remission induction therapy (RIT) were retrospectively assessed for the presence of ONFH. Results Among 186 AAV patients, 33 (18%) were diagnosed with ONFH. Among the patients with ONFH, 55% were asymptomatic and 64% had bilateral ONFH. Seventy-six per cent of ONFH joints were in precollapse stages (stage ≤2), whereas 24% of ONFH joints were in collapse stages (stage ≥3). Moreover, 56% of the precollapse stage joints were already at risk of future collapse (type ≥C-1). Even in asymptomatic ONFH patients, 39% of the precollapse stage joints were type ≥C-1. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH in AAV patients (OR 1.072, 95% CI 1.017 to 1.130, p=0.009). Rituximab use was a significant beneficial factor against ONFH (p=0.019), but the multivariate analysis rejected its significance (p=0.257). Conclusion Eighteen per cent of AAV patients developed ONFH, and two-thirds of the ONFH joints were already in collapse stages or at risk of future collapse. Prednisolone dose of ≥20 mg/day on day 90 of RIT was an independent risk factor for ONFH. A rapid reduction of glucocorticoids in RIT and early detection of precollapse ONFH by MRI may decrease and intervene ONFH development in AAV patients.
Background/Introduction: Recent ESC/AHA guidelines have modified the risk scoring system for ICD implantation in hypertrophic cardiomyopathy.An appropriate risk stratification may be relevant also at the end of ICD battery life when the decision to replace the device must be taken.Purpose: At the present time, no data are available from HCM patients who undergo an ICD replacement procedure.We evaluated the current ESC risk score to predict SD risk over 5 years in our population.Methods: Data from 38 pts with HCM from the DECODE registry were included in the present analysis.The SD risk score suggests: recommendation for ICD implant if SD risk 6% (high risk profile -HRp); implantation of ICD is based on physician discretion if SD risk is between 4% and 6% (intermediate risk profile -IRp); ICD is notrecommended if SD is < 4% (low risk profile -LRp).Decision on first ICD implantation was based on reference guidelines.Results: The median SDrs was 6.9 [3.8-11.6]:11 (29%) pts had a SDrs < 4%; 3 (8%) pts had an intermediate SDrs and 24 (63%) pts had a HRp.Pts characteristics at the time of ICD replacement were: mean age ¼ 56616 years; male gender ¼ 26 (68.4%); history of AF ¼ 19 (50%); median LVEF ¼ 55% [40.25-69.5]and NYHA class I ¼ 20 (52.6%).16 (42.1%)pts experienced an appropriate ICD therapy whereas 6 (15.8%) pts received an inappropriate ICD therapy before ICD replacement over a mean follow-up period of 5.662 years.No differences were found in terms of appropriate therapy among pts with a HRp and IRp to LRp: 11/24 (46%) pts for HRp group vs 5/14 (36%) pts for IRp/LRp group (p¼NS).After ICD replacement 5 (13.2%) pts experienced an appropriate ICD therapy whereas 2 (5.3%) pts received an inappropriate ICD therapy over a mean follow-up period of 378669 days, all in the HRp group. Conclusion:The current risk stratification tool for identifying patients with HCM indicated to ICD may exclude pts who are prone to receive life-threatening VT during ICD service life.However the risk-benefit ratio of elective ICD replacement may be different than that at the time of initial ICD implant.P1477
Currently, many space missions that use cryogenic equipment are being planned. In particular, high resolution sensors, such as transition edge sensors, require very low operating temperatures, below 100 mK. Adiabatic demagnetization refrigerator (ADR) systems are a useful tool for producing ultra-low temperatures in space because these devices can operate independently of gravity. The magnetic material is one of the most important components with respect to effectiveness of the cooling power. Thus, we could increase the cooling power using a magnetic material that has a large entropy change over the operating temperature range. Polycrystalline Gd2O2S (GOS), which was developed by Numazawa et al, can be used as such as a magnetic regenerator material. Furthermore, GOS has a very large specific heat and a magnetic phase transition temperature of about 5.2 K. These features make GOS suitable for use in the high temperature stage of an ADR. In this study, we measured and evaluated the physical properties of GOS for applications to ADRs.
We studied latent (mild) pulmonary encephalopathy in 14 patients with mild chronic respiratory insufficiency due to the sequelae of pulmonary tuberculosis. All of the patients were between 49 and 62 (mean age: 57.9). None of them had any impairment of daily activities and apparently had a clear consciousness. First, the P300 component evoked by auditory stimuli was examined. Immediately after that, the PO2, PCO2, pH were measured. Then the Hasegawa's dementia scale, the mini-mental state, the "Kanahiroi" test, Zung's depression score, digit span test were also assessed in the 14 patients. P300 components in 7 age-matched normal volunteers were also examined and compared with those in the 14 patients. The mean P300 latency in the patients were significantly prolonged compared with that in the normal volunteers (p less than 0.01). The P300 latency was well correlated with the PCO2, PO2, pH. The results of the "Kanahiroi" test also correlated with these parameters. We suggest that patients with mild respiratory insufficiency due to the sequelae of pulmonary tuberculosis often have latent (mild) pulmonary encephalopathy, and that P300 latency and the "Kanahiroi" test are very useful to detect and evaluate such latent pulmonary encephalopathy.
AimsFor successful ablation of ventricular outflow tract arrhythmia, estimation of its origin prior to the procedure can be useful. Morphology and lead placement in the right thoracic area may be useful for this purpose. Electrocardiography using synthesized right-sided chest leads (Syn-V3R, Syn-V4R, and Syn-V5R) is performed using standard leads without any additional leads. This study evaluated the usefulness of synthesized right-sided chest leads in estimating the origin of ventricular outflow tract arrhythmia.
Eleven cases of renovascular hypertension treated by the authors during the 10-year period from 1974 to 1984 are summarized in this paper, referring particularly to its etiology and prognosis. The causative diseases included 3 cases of atherosclerosis, 4 cases of fibromuscular dysplasia, 1 case of aortitis syndrome, 1 case of abdominal aneurysm, 1 case of renovascular thrombosis, and 1 case of unknown origin. Operations were given in 10 of the 11 cases i.e., 7 cases of nephrectomy and 3 cases of reconstructive surgery for renal blood-flow. The results of operations at discharge were 7 cases of blood pressure normalization, 2 cases of its improvement and 1 case of no change. There was no operative mortality. The outcome of long followup revealed that 2 of the 3 patients with atherosclerosis died in 9 months and 1 year and 10 months, respectively, due to cerebral hemorrhage and renal failure. However, the patients with other diseases maintained their health for 5 years and 5 months (mean observation period), with normal blood pressure or a mild hypertension. Sometimes, in patients with atherosclerosis in whom severe arteriosclerotic lesions already exist in the cardiovascular system, conservative therapy is better than surgical therapy. The indication for surgical therapy, should be made after considering the results of the angiotensin II analogue test.
